(1) The anti-estrous factor of
Research article
Some Characteristics of the Anti-Estrous Factor in Lithospermum . ∗
Paul A. Zahl
Abstract
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(1) The anti-estrous factor of
The gush of excess blood that appears in the venous outflow from an organ when the outflow pressure is suddenly lowered has been selected as an index of the distensibility of the venous system of that organ. With the aid of a new type of flow meter to quantitate venous outflow, this phenomenon has been studied in innervated hind legs of anesthetized dogs. The results indicate a relatively low distensibility in the venous system of the hind leg of the dog; the volume-pressure data demonstrating a fairly linear relationship in the venous pressure range of 0 to 20 cm of blood, with a trend toward even less distensibility at higher pressures.
Unlike the rat, the induction of deciduomata does not prolong pseudo-pregnancy in the mouse. The mechanism responsible for this marked species difference in response to apparently identical physiological conditions is obscure.
(1) Hemagglutinin production in response to inoculation with human erythrocytes has been investigated in thiamin- and biotin-deficient rats. (2) A moderate impairment of antibody response was observed in both deficiencies.
The process of wound healing has been observed in rats exhibiting severe deficiency of biotin, pyridoxin, or riboflavin. Marked impairment of rate and quality of healing was noted in the pyridoxin- and riboflavin-deficient groups. The biotin-deficient group showed only mild delay in healing.
The rate of hydrolysis of l-leucylglycylglycine by the cobalt activatable peptidase in human serum shows little variation in normal adults, but is increased in certain pathological states, particularly in fractures and postpartum infections.
A photometric method is described based on the gravimetric procedure of Butler and Tuthill in which the precipitated sodium zinc uranyl acetate is dissolved in water, giving a yellow color which is read with a suitable filter against a standard curve at 430 mμ. Phosphates in the normal urine were found to exert negligible interference. Recoveries and comparison values show the method to be more rapid and at least of equivalent accuracy with the gravimetric procedure.
The antibiotic Chloromycetin has been found to be only moderately bacteriostatic for virulent human type tubercle bacilli
When administered subcutaneously, Chloromycetin has been shown to be ineffective, whereas, when admixed with the diet in concentrations of 0.5 and 0.25%, it was slightly effective for the suppression of experimental murine tuberculosis.
1. An antibiotic, tentatively designated subtenolin, was isolated from a strain of
2. Although the antagonist displays its greatest activity against staphylococci, the growth of certain gram-positive as well as gram-negative organisms is inhibited.
3. The growth of
4. Subtenolin activity has been detected in urines recovered from intraperitoneally inoculated mice.
5. Acute toxicity studies show that the LD50 of subtenolin for mice inoculated intraperitoneally is 30 to 60 mg (30,000-60,000 units).
It may be seen from Table I that subtenolin is quite different chemically from other antibiotics such as streptomycin, penicillin G, gramicidin, and bacitracin. Subtenolin, bacitracin, bacillin, subtilin, and eumycin are products of various strains of
Subtenolin has a low molecular weight. Its chemical and physical properties indicate that it contains a resonating double bond, phenolic groups, a very active enolic group, and an aromatic aldehyde radical. This antibiotic gives typical color reactions such as the Molisch and enol reaction. These tests, and the indicator test shown in Table I, may be used in its identification. Although the antibiotic has not been obtained in a pure state, its chemical and antibiotic properties, particularly its stability in aqueous solution or when dry, make it an interesting object for further studies.
Rabbits given Dibenamine 12 to 24 mg/kg in propylene glycol or ethyl alcohol by vein show sudden respiratory arrest within 3 minutes of exposure to hypoxia (circa 5% O2 in helium).
Heterophile antibody agglutination, Kahn, and cold agglutinin tests were performed in 2 groups of patients with viral hepatitis. Sixteen out of 508 patients (3%) developed positive heterophile antibody tests with titers of 1:56 which were reduced to 1:7 or negative by absorption on boiled guinea pig kidney. A rise and/or fall in titer of antibody was demonstrable in serial weekly determinations. Out of 388 patients who were known not to have syphilis, 6 (1.5%) developed positive Kahn tests, and 10 others (2.5%) had doubtful tests. Two out of 323 patients had cold agglutinins present in a titer of 1:32.
The relatively small number of positive heterophile antibody agglutination and Kahn tests is in contrast to reports of others 2 5 who have found a considerably higher percentage of positive tests.
1. In addition to a favorable internal environment in the cell, light is necessary for the development of melanin in melanophores of intact scales.
2. Light passing directly through glass bottomed tanks onto the lower surface of the flounders was the most effective in producing melanophores. This means of illumination delivered the most intense light to the ventral surface of the fish and could be most accurately measured.
3. The use of opaque masks indicates that light affects the cell directly to produce melanin.
4. The melanination of regenerating scales is apparently not dependent upon the presence of light. Investigation of this special problem is being continued.
For the microscopic observation
This study indicates that the changes in the excretion of ascorbic acid are not accurate indications of utilization. The ingestion of both salts significantly lowered the mean plasma ascorbic acid content of the subjects indicating an interference with normal utilization. The reduced excretion of ascorbic acid with the ingestion of sodium bicarbonate both daily and in response to a test dose would seem therefore to represent more accurately increased destruction of ascorbic acid in the excretory process; and conversely, the increased excretion with ammonium chloride would seem to represent increased preservation in the excretory process.
1. Embryonic chicks were inhibited by the direct injection of 3-acetylpyridine into the yolk-sac. 2. It was shown that this inhibition could be reversed competitively by nicotinamide over the range of 2000 to 7000 γ per egg. 3. Evidence is presented showing that 4-day-old chick embryos have a very limited capacity to convert nicotinic acid to the corresponding amide. 4. Sublethal levels of 3-acetylpyridine are shown to cause a mal-development of the chick embryo.
In various buffers. MM virus was stable at room temperature only at neutral or alkaline reactions. When diluted virus was exposed at approximately pH 1.0 to neutrality the infectivity was diminished within twenty-four hours. There was a slower decrease in virus titer at pH 9 to 10. At pH 7 to 9, the virus was found to be stable for more than seven days. The deleterious effect of unfavorable pH was less for concentrated virus suspensions. MM virus was apparently more stable in distilled water acidified with hydrochloric or acetic acid than in acidified physiologic saline or in veronal-acetate buffer solutions of approximately the same pH value.
The experimental production of acute mild intestinal or gastric disturbance or both in man, tends to confirm the etiological role of
Previous work has shown that a meningoencephalom yet it is, sometimes with foci of demyelinization, may occur in monkeys, guinea pigs, and rabbits 2 to 9 weeks following the subcutaneous or intramuscular injection of brain tissue mixed with acid-fast bacilli in a water-in-oil emulsion. 1-6 In contirmatory work in this laboratory an ascending paralysis has developed in slightly niore than half of some 90 guinea pigs following the single subcutaneous injection of one cc of siniilar emulsions containing guinea pig, rabbit. human. or beef brain suspended 1:20 in 0.9:; saline. The illness usually began 15 to 31 days after injection. although it was delayed as long as 74 days in one case; the aniinals usually died within 10 days, although 3ome recovered and others remained paralyztd ior one to 2 months. Histological examination.; oi brain and qpinal cord removed from about 30 paralyzed guinea pigs in every case rewiled a patchy or diffuse perinscular inflammation. Predominantly lymphocytic in the leptonieninges and entire central nerious system most concentrated in the white matter. The evidence that this discase may represent an allergic reaction has been recently reviewed. 7 Further experiments now to be demibed have shown that the “antizen” responsible for this experimental disease is present in certain phosphatide-like extracts of brain tissue, in a preparation of “purified brain lipids,” and in optic nerve, which contains only white matter.
To learn about the nature of the “antigen,” various estracts of whole moist beef or human brain were made accordins to the outline of Page using acetone cold petrol ether cold 95% alcohel ether and warm pyridine.
It would appear that there exist differences in the reaction of the mouse and rat to experimentally induced hypothyroidism and hyperthyroidism, possibly dependent upon the relative thyroxin secretion rates of the two species.
(1) The effects of single and repeated convulsions induced by electroshock were observed in 6 chronic decorticated cats. (2) The seizures were characterized by a posture of general semiflexion with small amplitude rapid rhythmic movements of the limbs, jaws and facial musculature, interrupted by one or more short quiescent periods, terminating in running movements after which a more prolonged quiescent phase preceded recovery. Apnea occurred during the seizures and was followed by transitory hyperpnea. (3) Body temperature and pulse rate were not affected significantly. Righting reflexes returned a few minutes after each seizure. Licking reflexes were abolished for from 1 to 3 1/2 hours after each convulsion in 3 preparations. Sham rage in response to a non-nociceptive stimulus was unaffected or enhanced temporarily after each electroshock convulsion. Sham rage responses (chiefly facio-vocal) to nociceptive pressure stimuli applied to the tail were markedly reduced or abolished for from 1 to 2% hours after each electrically induced seizure. (4) No changes other than those noted after single electroshocks were noted after repeated electrically induced convulsions. (5) The electro-encephalographic patterns of electroshock convulsions in the decorticated preparations were characterized by bursts of relatively high voltage 2 to 21 per second rhythms separated by short silent intervals, frequently terminating in a steady 15 to 18 per second discharge before cessation of electrical activity. Slow and fast wave sequences appeared at times during the paroxysmal discharges and were more prominent in previously morphinized preparations. (6) Gross and microscopic studies of the remaining brains after completion of the experiments revealed no changes which could be ascribed to the electric currents used to evoke convulsions.
1. Chick embryos which were killed by chilling on the 3rd day of development and were thereafter maintained at 37°C for 16 days still contained living cells.
2.
3. The significance of these findings and some advantages inherent in this method are discussed.
Conventional histological techniques have been modified so that is is possible consistently to cut 0.2 micron sections for use with the electron microscope. The material must be doubly embedded in strong collodion and hard paraffin. The face of the block to be cut must be small, and the tilt of the knife must be precisely adjusted.
Procedures have been developed for partly or wholly removing the embedding media, and mounting the sections for the electron microscope.
Micrographs of rat liver sections show that the principal artefacts are due to fixation rather than subsequent treatments.
Human erythrocytes undergo lysis in the presence of tannic acid and human complement, even when cells and complement are obtained from the same blood sample. This reaction is dependent upon an optimal concentration of 0.7% sodium chloride, and an optimal concentration of between 0.06 and 0.03% tannic acid. When these substances are present in proper concentration, human complement can be titrated with reproducible results.
Specific fixation of human complement by three separate antigen-antibody systems has been demonstrated, employing homologous erythrocytes sensitized by tannic acid. Antibody titers determined by this method were comparable to those obtained in the standard complement fixation test.
Chloromycetin possesses considerable therapeutic activity in embryonated eggs and mice infected with the viruses of psittacosis or lymphogranuloma venereum. This activity is comparable in amount to that demonstrated by others for sulfadiazine and penicillin tested under similar conditions.
Tannic acid inhibits both hemagglutination and multiplication of influenza A virus.
Human salivary mucin and hog gastric mucin do not inhibit the hemagglutination induced by the PR8, LEE, and Swine strains of influenza virus and these mucins do not inhibit the multiplication of PR8 or LEE in the developing chick embryo. There was no turbidimetric or viscosimetric evidence of viral action on these mucins. Influenza virus was also unable to modify the conductivity of the human salivary mucin or the hog gastric mucin.
Anesthesia in the rat by means of nembutal or ether produces a hemodilution, as shown by both a decrease in the red cell numbers and in the specific gravity of the blood.
Skin tests with certain certified food dyes in patients sensitive to paraphenylenediamine suggest that eczematous hypersensitivity to paraphenylenediamine may not only cross over to azo-dyes used for the dyeing of leather and fabrics, or in ointments, but also to certain azo-dyes certified by the Food, Drug and Cosmetic Act of 1938 for use in foods, drugs and cosmetics. The implications of these findings are discussed.
1. Daily intramuscular injections of lung extract for two months preceding and following clamping of the renal artery and contralateral nephrectomy failed to prevent the development of hypertension in two dogs. 2. Pneumonectomy performed on 2 renal hypertensive dogs and pneumonectomy plus contralateral lobectomy on 2 other hypertensive animals did not alter their pressure levels. 3. The pressures of 2 normotensive dogs were not influenced by pneumonectomy, nor were the hypertensions subsequently produced by renal artery constriction and contralateral nephrectomy. 4. The results of these experiments suggest, but do not prove, that the lungs do not elaborate an antihypertensive substance and do not inactivate the pressor agent of experimental renal hypertension. 5. Further work is necessary to explain the pulmonary normotension of renal hypertensive dogs.
1. Pancreatic juice provides buffering material which serves to neutralize gastric content more effectively, but some degree of neutralization is attained from other secretions of the small intestine and its appendages.
2. No correlation is evident between the acidity of the duodenal content and the volume of pancreatic secretion.
The observation that lymphocytes from animals infected with certain bacteria are specifically destroyed by contact
Scleroderma (literally: ‘hardening of the skin’) occurs in two forms: diffuse and localized. The diffuse form is a progressive systemic disease of the connective tissue throughout the body 1 , 2 The localized form on the other hand appears clinically to be limited to the skin and is a much milder disease. In spite of numerous investigations, the pathogenesis of scleroderma remains obscure. Observations on the serum proteins have been limited to an occasional routine determination showing a decrease in the albumin /globulin ratio with little change in the value for total proteins 3 It seemed possible that a more detailed analysis by the Tiselius method of electrophoresis might yield additional information of value.
Results. In diffuse scleroderma, as shown in Table I, the albumin fraction of the serum proteins decreases and the y-globulin fraction increases, but no significant change occurs in the total protein value.
Acute hepatic damage in the dog, caused by chloroform intoxication, is followed by a pronounced and rapid decrease in plasma Ac-globulin concentration. This decrease is accompanied by a parallel decrease in plasma prothrombin concentration. Ac-globulin returns to normal values more quickly than does prothrombin.
1. The subcutaneous administration of large doses of sodium salicylate to rabbits well in advance of the initial contact with horse serum antigen prevents the development of arterial lesions.
2. The arterial lesions fail to develop even though circulating antibody is present in moderate quantity.
3. It is believed that the lesions fail to develop because there is no antigen-antibody reaction, and that this reaction can not take place because salicylate has prevented antigen from uniting with tissue cells.
Kynurenine and hydroxyanthran-ilic acid, which appear to be intermediates in the conversion of tryptophan to nicotinic acid by
1. A new technique of resolving and identifying the members of the B6 family of growth factors is described. It involves the use of paper partition chromatography coupled with a microbial indicator.
2. Using this method it has been demonstrated that pyridoxal undergoes a non-enzymatic transamination reaction even in the cold. Pyridoxal also appears to react reversibly with other amino acids.
3. The reaction between cysteine and pyridoxal differs from that with other amino acids in that one can demonstrate the formation of at least one adduct which moves more slowly on the chromatogram than does pyridoxamine. This reaction may produce a new form of vitamin B6 which may also have a transient existence in nature.
4. The technique described should prove of value as a means of establishing the purity of the various forms of vitamin BG used, in biological and biochemical studies.
5. The general technique employing paper partition chromatography and microbial indicators should be of value in resolving other multiform vitamins into their constituent parts.
1. Following phlebotomy in each of 4 normal male subjects, there was a transient fall in the plasma sodium concentration.
2. Following injections in 4 patients of a 25% solution of salt-poor human albumin solution, a similar fall in the plasma sodium concentration was noted.
3. It is concluded that sodium-poor fluid is added to the plasma, presumably from the intracellular space, folio wing hemorrhage, as well as following injection of salt-poor human albumin.
Observations were made on 11 subjects of varying ages to discover the environmental conditions necessary to initiate sweating in man. These studies, performed in a room designed for close control of temperature and humidity, indicate that an environmental temperature of 34.4° C and relative humidity of about 50% are essentially the threshold level for sweating in normal man resting in bed. Exercise and increased rate of heat production are associated with a proportionate lowering of the threshold.
The utilization of glutamic acid by
It has been observed that the addition of Tween 80 to solid and liquid media markedly stimulates the growth of minimus type diphtheria bacilli. This suggests a relationship between this wetting agent and the lipid-rich minimus organisms analogous to the relationship of the same agent to the lipid-rich tubercle bacilli, demonstrated by Dubos
The content of polysaccharide-depolymerizing substances (probably chiefly hyaluronidase) during allergic dermatitis (paraphenylenediamine) and heat-induced inflammation on guinea pig skin is markedly increased.
Within the past few years, reports have appeared on the effect of Cytochrome C∗ on tissue anoxia. From the clinical point of view, Proger and his co-workers have presented evidence that myocardial anoxia can be relieved by intravenous injection of Cytochrome C, as demonstrated by the prevention or reversal of the electrocardiographic changes induced by breathing 10% oxygen. 1 It is their contention that, under such circumstances, Cytochrome C enhances the uptake of oxygen by the myocardium.
Another method of testing the effect of a drug on myocardial anoxia is to determine the capacity for effort without pain in patients who have angina pectoris brought on by effort. Since this method depends on a subjective end-point, it is necessary to use careful controls and a completely “blind” technique, as described by Gold and his coworkers, in order to eliminate variable psychosomatic effects. 2 This method has been used by us in an evaluation of the effect of intravenous aminophylline on angina of effort, and it proved to be a satisfactory investigative technique. 3
The subjects of the study were all selected from the active attendance of the Cardiac Clinic. All of them had either arteriosclerotic or hypertensive heart disease or a combination of both, and all presented the symptom of chest pain on effort. No patients were included in this study who had spontaneous chest pain unrelated to effort, excitement, heavy meals, or very cold weather. Also excluded were patients who showed any clinical evidence of congestive failure.
The method consisted of determining the subject's capacity for effort without pain by having him walk back and forth over a standard set of steps until the onset of his usual type of chest pain. The rate of walking was set by the subject himself, and in any subsequent tests on that same subject, he was kept to the same rate.
The evidence obtained from the actions of Lanatoside C upon the embryonic duck heart indicated that such a heart exhibits a “digitalis effect” with no fixed latent period as described in previous studies. It would appear that if a sufficient quantity of digitalis glycoside is present, a “digitalis effect 1 may be expected almost immediately.
A study of 15 normal subjects has been performed by using fluorocardiog-raphy, a method which permits recording on a continuous film of the pulsations of various cardiovascular structures revealed by the x-ray. (a) The tracing of the ascending aorta presents a typical pattern which partly is due to transmission of intraventricular pressure and partly to motions of the aortic root connected with ventricular systole and diastole. (b) It is possible to record in certain cases a tracing of the pulmonary veins. Its most typical feature is a positive wave during presystole, (c) The velocity of the pulse wave in the lesser circulation is much lower than in the greater circulation. It is more rapid in the smaller branches than in the stems of the pulmonary artery. Average figures are given, (d) The tracing of the pulmonary parenchyma is the equivalent of a pie thy sinogram. While the rise and the ascending branch of the wave are of arterial pulmonary origin, the peak and the descending branch of the wave are probably of venous pulmonary origin.
A strain of
A constant rate of potassium excretion, dissociated from filtered load, occurring after salyrgan administration suggested a tubular secretory mechanism located, presumably, in the distal tubule. The presence of such a mechanism has been demonstrated by the intravenous administration of hypertonic KC1 solutions which yielded rates of potassium excretion considerably above the rates of filtration of potassium at the glomerulus.
K clearances in excess of creatinine or thiosulfate clearances, under the conditions of these experiments, are interpreted as- evidence that all of the K excreted in the urine cannot be accounted for by the nltration-reabsorption theory alone, but that tubular secretion of K also occurs. In the experiments on urea diuresis, urea clearances never exceeded creatinine clearances, and the ratios agreed with the observations of Shannon. 8 It is a reasonable hypothesis that during urea diuresis the secretion of K becomes apparent because its normal tubular reabsorption is hindered. The present data are insufficient to define the mechanisms involved in the secretory process or to demonstrate the relative magnitude of the processes of filtration, reabsorption and secretion in the renal excretion of K. Further work is in progress.
The performance of agglutination tests, using the blood cells of mice of 5 inbred strains and 8 types of F1 and F2 hybrid mice, have shown that human sera can be differentiated, apart from the usual intra-group reactions, by their ability to agglutinate mouse erythrocytes. The differentiation of human sera on this basis depended on the presence or absence of a specific agglutinin (Mo agglutinin). It was found to bear no specific relationship to either the A-B-0 blood groups or the Rh factor. Five of the 37 human sera tested (approximately 14%) did not contain the Mo agglutinin. Mouse erythrocytes adsorbed the Mo agglutinin but not α and β agglutinins or the rabbit cell agglutinin. Human erythrocytes of the a and β group and rabbit red cells adsorbed their specific agglutinins, but not the Mo agglutinin.
Three starch preparations were fed to a total of 240 animals. The rates of hydrolysis, emptying and absorption are closely related. Increasing the size of the test meal increases these rates. The data were obtained under conditions permitting the elimination of forced feeding.
The proteins of whole egg, whole egg white, and yolk, were prepared and analyzed for cystine, methionine, phenylalanine, tryptophane, threonine, arginine, histidine, lysine, sulfur, and nitrogen. These proteins were incorporated into diets at a 10% level and fed to young rats. The protein efficiency ratio (gain in weight per gram of protein ingested) was determined after a 2-week feeding period. Commercial preparations of wmole egg and whole white protein were similarly analyzed and their PE ratio determined. The PE ratio of the whole white protein was higher than that of either the whole egg or the yolk proteins. The PE ratio of the commercial whole white protein was almost as high as that of the laboratory prepared sample. The PE ratio of commercial whole egg protein was markedly lower than that of the laboratory prepared sample. The amino acid content of all the whole egg proteins wTere quite similar with the exception of the cystine content of the commercial samples which was lower than that of the laboratory samples. When the commercial whole egg protein II was reenforced with 0.25% cystine the PE ratio was not improved. Other factors in addition to the amino acid content apparently play a role in the biological value of proteins.
Many reports have been published concerning the effects of potassium on the electrocardiogram in various clinical states 1-13 and in experimental animals. 14-17 These have been concerned chiefly with its effect upon the T-wave. Relatively little attention has been devoted to its effect upon the QRS complex except in those cases in which toxic doses were given. Inspection of the published records, however, shows that in many instances a reduction in the size of the QRS deflections followed the administration of this drug. We refer particularly to instances in which potassium was given to patients with hypertensive heart disease. In the articles referred to the QRS changes were not mentioned in the texts or legends. In fact in some of these it was reported that no change in the form of these deflections took place. 4 , 13 In a previously reported study 18 sodium restriction in hypertensive vascular disease was followed by retrogressive electrocardiographic changes unaccompanied by a significant change in blood pressure. This raised the question as to whether a relative increase in tissue potassium secondary to sodium restriction was responsible for these electrocardiographic phenomena. Consequently the effect of potassium alone upon the electrocardiogram in cases of hypertension was investigated. Potassium in the form of the chloride, dibasic phosphate, or citrate was administered, on 25 occasions, to patients with abnormal electrocardiogams characteristic of hypertensive vascular disease, and, on ten occasions, to normal subjects. Electrocardiograms were obtained immediately before and at times ranging from 15 minutes to 3 hours after the ingestion of 5 to 20 g of one of the potassium salts mentioned. In several instances 10 to 24 g of potassium salts daily had been prescribed previously and the patient had continued on this dosage up to the time of the test.
An improved method for determining the nitrogen washout time with measurement of the various subdivisions of the pulmonary volume is described. The method is proving helpful in the differential diagnosis of pulmonary disease and in estimating the functional changes produced by intrathoracic operations.